Keratin materials, and in particular the head of hair and the skin, comprise epithelial stem cells which, generally, in addition to their pluripotent capacity, are capable of differentiating into various cells which make up the tissues of the body and of self-renewing. These functionalities are necessary for regenerating the tissues, but can undergo certain modifications or dysfunction over time.
In particular, the human head of hair represents a collection of approximately 150 000 hairs. Each one of them is generated by a specialized secondary component of the skin, a truly autonomous organ, the hair follicle. The growth of the hair and the renewal thereof is not a continuous process, it been determined by the activity of the hair follicles and their matrix environment. The activity of such follicles is cyclic and comprises essentially four phases. Indeed, the follicle goes successively from a growth phase with production of the hair shaft (anagen phase), to a rapid involution phase (catagen phase), then to a resting phase with hair loss (telogen phase), which precedes a regeneration (neogen) phase so as to once again arrive at the anagen phase. The anagen phase, an active or growth phase during which the hair gets longer, lasts several years. The very short catagen phase lasts a few weeks. The telogen phase or resting phase lasts a few months. At the end of this resting period, the hairs fall out and another cycle recommences. The head of hair is therefore undergoing constant renewal and, out of the approximately 150 000 hairs which make up a head of hair, approximately 10% are resting and will be replaced over the coming months.
Natural hair loss can be estimated, on average, at a few hundred hairs per day for a normal physiological state. This constant physical renewal process undergoes a natural change during aging, the hairs become thinner and their cycles become shorter.
Various causes can, however, lead to considerable temporary or definitive hair loss. Hair loss, in particular alopecia, is essentially caused by disruptions of hair renewal. These disruptions lead, initially, to shortening of the anagen phase and gradual thinning of the hair, and then a decrease in the amount thereof. Gradual miniaturization of the bulbs occurs, with, in conjunction, isolation thereof through gradual thickening of the collagen matrix of the outer connective sheath. The revascularization around the hair follicle is therefore made more difficult with each cycle. The hairs regress, and miniaturize until they are no more than a non-pigmented down, and this phenomenon leads to gradual depletion of the head of hair.
Areas are preferentially affected, in particular the temporal or frontal lobes in men, and in women, diffuse alopecia of the crown of the head is observed.
The term alopecia also covers an entire family of hair follicle damage resulting in the end in partial or general definitive hair loss. This is more particularly androgenic alopecia. In a considerable number of cases, premature hair loss occurs in genetically predisposed individuals, it is then androchronogenetic alopecia; this form of alopecia concerns in particular men.
It is, moreover, known that certain factors, such as a hormonal imbalance, a physiological stress or malnutrition, can accentuate the phenomenon. In addition, hair loss or modification may be connected to seasonal phenomena.
Generally, any factor which influences these processes, namely acceleration of cycle frequency, gradual bulb miniaturization, gradual thickening of the perifollicular collagen matrix, thickening of the outer connective sheath, and a decrease in vascularization, will have an effect on hair follicle growth.
The hair follicle is structurally composed of two distinct compartments: an epithelial compartment and a dermal (mesenchymal) compartment, and the interaction of these two compartments is essential for hair morphogenesis and regrowth and also for maintaining the follicular cycle. The maintaining of the functionality of the epithelial compartment is dependent on the presence and on the activity of various stem cell reservoirs. A first reservoir of epithelial stem cells was identified in a region called the “bulge” in rodents (Cotsarelis G, Sun T T, Lavker R M. (1990) Cell 61: 1329-1337). Since this first discovery, other reservoirs of keratinocyte stem cells have been identified, always in rodents. These stem cells play an essential role in follicle morphogenesis, but they are also involved in epidermal repair in the event of injury. Studies on human follicles are much more rare, but reveal at least two reservoirs of epithelial stem cells characterized by the expression of keratin 19, which are nested in the outer root sheath (ORS) of the follicle (upper third and lower third) (Commo S, Gaillard O, Bernard B A. (2000) Differentiation 66:157-164).
Although these stem cell reservoirs are acknowledged to be absolutely essential for maintaining and regenerating the hair follicle, there is, at the current time, very little knowledge regarding the modification of these cell populations with age and/or with the beginning and the progression of alopecia (all types of alopecia included). It has recently been demonstrated that hair loss in men with alopecia is accompanied by a disappearance not of stem cells, but rather of certain populations of progenitor cells (more active, proliferative cells). These results suggest that alopecia could be linked to a problem of follicle stem cell activation or else of the expression of the complete regenerative potential of the progenitor cells (L A Garza et al. (2011) J Clin Invest. 121: 613-622).
The identification of technical solutions which allow better preservation of the functionality/activity of follicular epithelial stem cells would therefore be very important with a view to preserving hair quality, density and shape throughout an individual's life.
Given the importance of the microenvironment (niche) in the regulation of the activity and of the functionality of stem cells in diverse and varied tissues, the inventors have undertaken studies in order to identify environmental factors which could regulate the activity of epithelial stem cells.
To do this, in addition to investigations on follicular epithelial stem cells, the inventors have at the same time broadened their investigation to skin epithelial cells.